The Phase 3 INVIGORATE Trial of Reproxalap in Patients with Seasonal Allergic Conjunctivitis

Abstract

Purpose

There is an unmet need for new treatments for allergic conjunctivitis.

Objective

To assess the activity of reproxalap, a novel reactive aldehyde species modulator, in a real-world model of seasonal allergen exposure.

Methods

The INVIGORATE Trial, a prospective, quadruple-masked, vehicle-controlled, crossover, sequence-randomized Phase 3 trial, tested the efficacy of reproxalap in adults with a history of moderate to severe allergic conjunctivitis, ragweed pollen allergy, and allergen chamber-induced ocular itching and redness. Patients were randomly assigned (1:1) to receive 0.25% reproxalap ophthalmic solution or vehicle, followed by a 2-week washout period before crossing over to the other test article. The primary endpoint was ocular itching from 110 to 210 minutes after chamber entry; the key secondary endpoint was ocular redness over the chamber duration (0–4 scales for both endpoints).

Results

Of the 95 randomly assigned patients, 89 completed all visits (reproxalap to vehicle: n = 46; vehicle to reproxalap: n = 43). Primary and key secondary endpoints were met: reproxalap significantly reduced ocular itching (mean [SE]: −0.50 [0.03], p < 0.001) and redness (−0.14 [0.01], p < 0.001) relative to vehicle. Responder analyses confirmed the clinical relevance of both end points. Reproxalap was safe and well tolerated. No clinically significant changes in safety assessments were observed. No serious or severe treatment-emergent adverse events (TEAEs) were reported. The most commonly reported TEAE was mild and transient installation site irritation after reproxalap versus vehicle administration.

Conclusion

In this well-controlled allergen chamber trial, reproxalap was statistically superior to vehicle across typical symptoms and signs of allergic conjunctivitis.

Trial Registration

NCT04207736.

Keywords:

• allergic conjunctivitis
• reactive aldehyde species
• reproxalap
• ocular itching
• ocular redness

Data Sharing Statement

Due to commercial and legal restrictions, supporting data is not available.

Acknowledgments

Data included in this manuscript were presented at the 2022 Annual Meeting of the American Academy of Optometry; October 26–29, 2022; San Diego, CA, USA.

Disclosure

The authors have made the following disclosures: C.E.S.: Consultant – Novartis, Allergan, TearLab, Sun Pharma, Bruder, BlephEx, Kala Pharmaceuticals, Quidel, Dompe, Johnson & Johnson Vision, Essiri Labs, Tarsus Pharmaceuticals, Oyster Point Pharma, Visionology, CSI Dry Eye, Aerie, Eyebiotech, Versea, Bausch & Lomb and Aldeyra Therapeutics; Stock ownership – Essiri Labs and Visionology. K.K.N.: Consultant – Allergan/AbbVie, Axim, Aerie, Alcon, Alderya, Azura, Bruder, Bausch + Lomb, Cavalry, Dompe, HanAll Biopharma, Kala Pharmaceuticals, Novartis, Shire, Takeda, Nicox, Novaliq, Palatin, Osmotica/RVL, Oyster Point Pharma, Sight Sciences, Sun Pharma, Thea, Tarsus Pharmaceuticals, Topivert, Trukera, Versea, Visionology, and Xequel; Research: Science Based Health, TearScience, Sylentis, Kowa, and Aramis; Grants – Allergan, Kala Pharmaceuticals, NIH, and TearScience; Stock ownership – Alcon Vision/Tear Film Innovations, Axim, and Visionology. She also reports consulting (last 2 years) in the area of Dry Eye/MGD (not ocular allergy) for Abbvie, Allergan, Aerie, Alcon, Axim, Alderya, Azura, Bausch + Lomb Bruder, Cavalry, Dompe, HanAll Bio, Novartis, Shire, Takeda, Osmotica, RVL, Nicox, Novaliq, Oyster Point Pharma, Palatin, Thea, Tarsus, TopiVert, TearSolutions, Trukera, Versea, Xequel; Research for Science Based Health, TearScience, Sylentis, Kowa, and Aramis. J.R.L.: Consultant — Alcon, AscuelaTech, Allergan/AbbVie, Avellino, Aldeyra, Dompé, Envision Biomedical, Kala, Novartis, AOS, Scope, Sight Sciences, Sun Pharma, Tarsus, Quidel, Horizon, Aerie, Ocular Therapeutix, Trukera, Orasis, Oyster Point, Viatris, and Zeiss. T.C.B. Employee – Aldeyra Therapeutics; Patent interests (US11197821 and US9687481) – Aldeyra Therapeutics; Stock ownership – Aldeyra Therapeutics and Evoke Pharma. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was supported by Aldeyra Therapeutics, Inc., Lexington, MA, USA. The sponsor participated in the design and implementation of the study, the analysis and interpretation of the data, and the preparation, review, and approval of the manuscript.